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Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement. Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy. One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.

Background: Frontal lobe epilepsy is pharmacoresistant in 30% of cases, constituting 10-20% of epilepsy surgeries. For cases of no lesional epilepsy (negative MRI), frontal lobectomy is a crucial treatment, historically involving Frontal Anatomical Lobectomy (AFL) with a 33.3% complication risk and 55.7% seizure control., Methods: We describe Frontal Functional Lobectomy (FFL), in which the boundaries are defined on the patient's functional cortico-subcortical areas, recognized with advanced intraoperative technologies such as tractography and navigated transcranial magnetic stimulation (nTMS)., Conclusions: The FFL allows for a broader resection with a lower rate of postoperative complications than the AFL., (© 2024. The Author(s).)

Objective: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy., Methods: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4)., Results: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002)., Interpretation: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148., (© 2024 American Neurological Association.)

Summary: Current preoperative evaluation of epilepsy can be challenging because of the lack of a comprehensive view of the network's dysfunctions. To demonstrate the utility of our multimodal neurophysiology and neuroimaging integration approach in the presurgical evaluation, we present a proof-of-concept for using this approach in a patient with nonlesional frontal lobe epilepsy who underwent two resective surgeries to achieve seizure control. We conducted a post-hoc investigation using four neuroimaging and neurophysiology modalities: diffusion tensor imaging, resting-state functional MRI, and stereoelectroencephalography at rest and during seizures. We computed region-of-interest-based connectivity for each modality and applied betweenness centrality to identify key network hubs across modalities. Our results revealed that despite seizure semiology and stereoelectroencephalography indicating dysfunction in the right orbitofrontal region, the maximum overlap on the hubs across modalities extended to right temporal areas. Notably, the right middle temporal lobe region served as an overlap hub across diffusion tensor imaging, resting-state functional MRI, and rest stereoelectroencephalography networks and was only included in the resected area in the second surgery, which led to long-term seizure control of this patient. Our findings demonstrated that transmodal hubs could help identify key areas related to epileptogenic network. Therefore, this case presents a promising perspective of using a multimodal approach to improve the presurgical evaluation of patients with epilepsy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Objective: Neuroimaging studies reveal frontal lobe (FL) contributions to memory encoding. Accordingly, memory impairments are documented in frontal lobe epilepsy (FLE). Still, little is known about the structural or functional correlates of such impairments. Particularly, material specificity of functional changes in cerebral activity during memory encoding in FLE is unclear., Methods: We compared 24 FLE patients (15 right-sided) undergoing presurgical evaluation with 30 healthy controls on a memory fMRI-paradigm of learning scenes, faces, and words followed by an out-of-scanner recognition task as well as regarding their mesial temporal lobe (mTL) volumes. We also addressed effects of FLE lateralization and performance level (normal vs. low)., Results: FLE patients had poorer memory performance and larger left hippocampal volumes than controls. Volume increase seemed, however, irrelevant or even dysfunctional for memory performance. Further, functional changes in FLE patients were right-sided for scenes and faces and bilateral for words. In detail, during face encoding, FLE patients had, regardless of their performance level, decreased mTL activation, while during scene and word encoding only low performing FLE patients had decreased mTL along with decreased FL activation. Intact verbal memory performance was associated with higher right frontal activation in FLE patients but not in controls., Significance: Pharmacoresistant FLE has a distinct functional and structural impact on the mTL. Effects vary with the encoded material and patients' performance levels. Thus, in addition to the direct effect of the FL, memory impairment in FLE is presumably to a large part due to functional mTL changes triggered by disrupted FL networks., Plain Language Summary: Frontal lobe epilepsy (FLE) patients may suffer from memory impairment. Therefore, we asked patients to perform a memory task while their brain was scanned by MRI in order to investigate possible changes in brain activation during learning. FLE patients showed changes in brain activation during learning and also structural changes in the mesial temporal lobe, which is a brain region especially relevant for learning but not the origin of the seizures in FLE. We conclude that FLE leads to widespread changes that contribute to FLE patients' memory impairment., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Mild malformation with oligodendroglial hyperplasia (MOGHE) is a recently described clinicopathologic entity, associated with drug-resistant epilepsy and extensive epileptogenic networks. Knowledge is accumulating about particular electroclinical phenotypes, correlations with imaging, and potential prognostic significance for surgical outcomes. The study adds relevant information by documenting the presence of a hyperkinetic frontal lobe seizure phenotype in adolescents and an epileptic encephalopathy phenotype in young children., Methods: Five cases were subjected to a structured presurgical evaluation protocol, including EEG-FMRI, chronic and acute invasive EEG, subjected to frontal lobe surgery with postoperative follow-up between 15 months and 7 years., Results: In the two adult cases, surface EEG demonstrated lateralized widespread frontal lobe epileptogenicity and hyperkinetic semiological features. MRI demonstrated cortical white matter blurring and deeper white matter abnormalities. EEG-FMRI suggested concordant frontal lobe involvement. iEEG demonstrated a widespread frontal lobe epilepsy network. The three young children demonstrated a diffuse epileptic encephalopathy phenotype, with nonlocalizing, nonlateralizing surface EEG, and "spasms" as the main seizure type. MRI demonstrated extensive frontal lobe subcortical gray and white matter abnormalities, consistent with MOGHE literature for this age, while EEG-FMRI, in 2/3, demonstrated concordant frontal lobe involvement. They did not undergo chronic iEEG, and the resection was assisted by acute intraoperative ECoG. All cases were subjected to extensive frontal lobectomies with Engel class IA (2/5), IB (1/5), and IIB (2/5) outcomes., Significance: The study confirms the presence of frontal lobe epilepsy and epileptic encephalopathy phenotypes, in accordance with epilepsy phenotypes already described in MOGHE literature. Presurgical evaluation studies, including EEG-FMRI, can provide strong lateralizing and localizing evidence of the epileptogenic networks involved. All responded favorably to extensive frontal lobe resections, despite widespread epileptic activity recorded by surface and intracranial EEG pre- and postoperatively; an epileptic encephalopathy phenotype, in the first years of life, should not discourage such a resection., (© 2023 International League Against Epilepsy.)

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: Decision-making is crucial to daily life and can impact our society as well as economic conditions. Although the frontal lobes have been identified as important for decision-making, this capacity has only been studied to a limited extent in frontal lobe epilepsy and not at all after frontal lobe resection (FLR) for epilepsy. This study aimed to explore decision-making under ambiguity after FLR for epilepsy., Methods: Fourteen patients having undergone FLR for epilepsy completed the Iowa Gambling Task (IGT) which is a widely used tool to measure decision-making under ambiguity. Iowa Gambling Task scores included in the analysis were: total net score, separate scores from five blocks across the test, and a change score (last block of IGT minus first block). A group of healthy controls (n = 30) was used as a comparison. Associations between IGT and standardized neuropsychological methods for assessment of executive functions, self-rating questionnaires of mental health, fatigue, and behavior linked to frontal lobe dysfunction were also investigated., Results: The patient group performed inferior to controls at the final block of the IGT (p =.001).A group difference in IGT change scores was found (p =.005), reflectingthe absence of a positive change in performance over time for the FLR group compared to the control group. Correlations with tests of executive functions as well as self-rating scales were mainly statistically nonsignificant., Conclusions: This study shows that patients having undergone FLR for epilepsy have difficulties with decision-making under ambiguity. The performance illustrated a failure to learn throughout the task. Executive as well as emotional deficits may impact decision-making processes in this patient group and need to be considered in further studies. Prospective studies with larger cohorts are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the ability of semiology alone in localising the epileptogenic zone (EZ) in people with frontal lobe epilepsy (FLE) who underwent resective surgery., Methods: We examined data on all individuals who had FLE surgery at our centre between January 01, 2011 and December 31, 2020. Descriptions of ictal semiology were obtained from video-EEG telemetry reports and presurgical multidisciplinary meeting summaries. The putative EZ was represented by the final site of resection. We assessed how well initial and combined set-of-semiologies correlated anatomically with the EZ, using a semiology visualisation tool to generate probabilistic cortical heatmaps of involvement in seizures., Results: Sixty-one individuals had FLE surgery over the study period. Twelve months following surgery, 28/61 (46%) were completely seizure-free, with a further eight experiencing only auras. Comparing the semiology database with the putative EZ, combined set-of-semiology correctly lateralised in 77% (95% CI: 69-85%), localised to the frontal lobe in 57% (95% CI: 48-67%), frontal lobe subregions in 52% (95% CI: 43-62%), and frontal gyri in 25% (95% CI: 16-33%). No difference in degree of correlation was seen comparing those with ongoing seizures 12 months after surgery to those seizure free., Significance: Semiology alone was able to correctly lateralize the putative EZ in 77%, and localise to a sublobar level in approximately half of individuals who had FLE surgery. Semiology is not adequate alone and must be combined with imaging and EEG data to identify the epileptogenic zone., Competing Interests: Conflict of Interests None., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Sampling the insulo-opercular region with invasive recordings is crucial given the importance of this region in epileptic networks and a variety of electroclinical presentations. However, implantation of the insulo-opercular region via stereoelectroencephalography (sEEG) is considered technically challenging given complex vascular and gray matter relationships in this region. We investigated the safety of insulo-opercular sEEG exploration in children and young adults using standard sEEG approaches: (1) orthogonal insulo-opercular (including the pseudo-orthogonal insulo-opercular approach) and (2) medial-lateral insular oblique approach., Methods: We performed a retrospective cohort study of 30 consecutive patients who underwent 33 sEEG implantations. All patients had drug-resistant focal epilepsy, were between the ages of 4 and 21, and were operated at one institution between January 2019 and March 2021. Medical records and neuroimaging were reviewed. Hemorrhage, infection, and other complications were considered as outcome variables., Results: A total of 519 electrodes were placed. Eighty-one were placed orthogonally into the temporal operculum, 53 orthogonally into the frontal operculum, and 19 obliquely into the insula. sEEG electrodes localized seizure onset to the insulo-opercular region in eight patients, leading to a resection three times, an ablation four times, and one peri-insular hemispherectomy. Of the 519 electrodes placed, none of them exhibited hemorrhage or serious complications. Of the 153 electrodes placed into the insula, none had any permanent deficits or complications and one had minor bleeding due to the electrode breaking., Significance: These results demonstrate that the orthogonal (including pseudo-orthogonal) and medial approaches to sampling the insula are safe., (© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Resective surgery for selected individuals with frontal lobe epilepsy can be effective, although multimodal outcomes are less established than in temporal lobe epilepsy. We describe long-term seizure remission and relapse patterns, psychiatric comorbidity, and socioeconomic outcomes following frontal lobe epilepsy surgery., Methods: We reviewed individual data on frontal lobe epilepsy procedures at our center between 1990 and 2020. This included the presurgical evaluation, operative details and annual postoperative seizure and psychiatric outcomes, prospectively recorded in an epilepsy surgery database. Outcome predictors were subjected to multivariable analysis, and rates of seizure freedom were analyzed using Kaplan-Meier methods. We used longitudinal assessment of the Index of Multiple Deprivation to assess change in socioeconomic status over time., Results: A total of 122 individuals with a median follow-up of seven years were included. Of these, 33 (27 %) had complete seizure freedom following surgery, with a further 13 (11 %) having only auras. Focal MRI abnormality, histopathology (focal cortical dysplasia, cavernoma or dysembryoplastic neuronal epithelial tumor) and fewer anti-seizure medications at the time of surgery were predictive of a favorable outcome; 67 % of those seizure-free for the first 12 months after surgery never experienced a seizure relapse. Thirty-one of 50 who had preoperative psychiatric pathology noticed improved psychiatric symptomatology by two years postoperatively. New psychiatric comorbidity was diagnosed in 15 (13 %). Persistent motor complications occurred in 5 % and dysphasia in 2 %. No significant change in socioeconomic deciles of deprivation was observed after surgery., Significance: Favorable long-term seizure, psychiatric and socioeconomic outcomes can be seen following frontal lobe epilepsy surgery. This is a safe and effective treatment that should be offered to suitable individuals early., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Stereotactic ablation surgeries including radiofrequency thermocoagulation (RFTC) and laser interstitial thermal therapy are recent less invasive treatment methods for insular epilepsy. Volume-based RFTC after stereoelectroencephalography was first proposed by a French group as a more effective method for seizure relief in insular epilepsy patients than stereoelectroencephalography-guided RFTC., Objective: To describe the feasibility and technical details about volume-based RFTC in patients with insulo-opercular epilepsy., Methods: We successfully treated 3- and 6-year-old patients with medically refractory insulo-opercular epilepsy with volume-based RFTC, in which the target volume of coagulation was flexibly designed by combining multiple spherical models of 5-mm diameter which is smaller than reported previously., Results: The insula was targeted by oblique trajectory from the frontoparietal area in one case, and the opercular cortex was targeted by perpendicular trajectories from the perisylvian cortex in the other case. The use of the small sphere model required more trajectories and manipulations but enabled more exhaustive coagulation of the epileptogenic zone, with 70% to 78% of the planned target volume coagulated without complications, and daily seizures disappeared after RFTC in both patients., Conclusion: Volume-based RFTC planned with small multiple sphere models may improve the completeness of lesioning for patients with insulo-opercular epilepsy. Careful planning is necessary to reduce the risks of vascular injuries., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background and Objectives: Cingulate epilepsy (CE) is a rare type of focal epilepsy that is challenging to diagnose because of the polymorphic semiology of the seizures, mimicking other types of epilepsy, and the limited utility of scalp EEG., Methods: We selected consecutive patients with drug-resistant CE who were seizure-free after surgery, with seizure onset zone (SOZ) confirmed in the cingulate cortex (CC) by histology or stereo EEG. We analyzed subjective and objective ictal manifestations using video recordings and correlated semiology with anatomical CC subregion (anterior, anterior middle, posterior middle, and posterior) localization of SOZ., Results: We analyzed 122 seizures in 57 patients. Seizures were globally characterized by complex behaviors, typically natural seeming and often accompanied by emotional components. All objective ictal variables considered (pronation of the body or arising from a lying/sitting position, tonic/dystonic posturing, hand movements, asymmetry, vocalizations, fluidity and repetitiveness of motor manifestations, awareness, and emotional and autonomic components) were differently distributed among CC subregions ( p < 0.05). Along the rostro-caudal axis, fluidity and repetitiveness of movement, vocalizations, body pronation, and emotional components decreased anterior-posteriorly, whereas tonic/dystonic postures, signs of lateralization, and awareness increased. Vestibular and asymmetric somatosensory, somatosensory, and epigastric and enteroceptive/autonomic symptoms were distributed differently among CC subregions ( p < 0.05). Along the rostro-caudal axis, vestibular, somatosensory, and somatosensory asymmetric symptoms increased anterior-posteriorly., Discussion: CE is characterized by a spectrum of semiologic manifestations with a topographic distribution. CE semiology could indicate which cingulate sector is primarily involved., (© 2022 American Academy of Neurology.)

Frontal lobe epilepsy (FLE) is the second most frequent type of epilepsy and the surgical outcome depends on the etiology. For instance, patients with posttraumatic FLE (PTE) have a worse surgical outcome compared to patients with FLE related to a tumoral lesion (TL). The present study focuses to determine if the FLE etiology is associated with the P-glycoprotein (P-gp) expression, a condition associated with drug resistance. P-gp expression and cellular localization were determined by Western Blot and immunohistochemical experiments in cortical brain samples obtained from patients with PTE (n = 5), TL (n = 5), and autopsies (n = 5). The neuronal count was estimated by Nissl and stereology procedure. Results showed that the autopsies tissue showed a neuronal count of 3514 ± 304.2 neurons per mm 3 . The P-gp expression ratio was 0.33 ± 0.02. Its expression was found in endothelial cells. Negligible P-gp expression was detected in neurons and astrocytes. Compared to the autopsies group, the TL group showed no changes in the neuronal count but, there was a decreased P-gp expression ratio (46%, p < 0.05). P-gp was located mainly in neurons, slight in astroglial, and endothelial cells. The PTE group showed a similar P-gp expression ratio compared to the autopsies group. P-gp was expressed in neurons, astrocytes, and endothelial cells in these samples. However, experiments revealed a high P-gp expression in a lower neuronal count (38%, p < 0.05 vs autopsy group). The present study reveals that patients with PTE present neuronal P-gp overexpression. This finding could underlie their worst surgical outcome., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A 42-year-old male had intractable hyperkinetic seizure since childhood. Bottom-of-sulcus dysplasia was shown by MRI to be most likely an ictal focus, whereas ictal semiology suggested possible focus in the left frontal cortex. Scalp-recorded EEG could not delineate ictal EEG change at all partly because of violent hyperkinetic seizure, and thus intracranial EEG study by epidural electrodes was conducted as the best procedure for the safety concern. It showed ictal focus over the bottom-of-sulcus dysplasia and thus it was completely resected with seizure free more then 20 years until now. It was concluded that epidural electrodes are regarded as safe invasive recording method especially for violent hyperkinetic seizure, and that can provide us with essential information before epilepsy surgery.

Objective: In this study, we investigate the seizure outcomes of temporo-parieto-occipital (TPO) and frontal disconnections or resections in children with drug-resistant epilepsy (DRE) in order to determine factors which may predict surgical results., Methods: Children with DRE, who underwent either TPO or frontal disconnection or resection at Great Ormond Street Hospital for Children between 2000 and 2017, were identified from a prospectively collated operative database. Demographic data, age at surgery, type of surgery, scalp EEGs and operative histopathology were collected. Magnetic resonance imaging (MRI) was assessed to determine completeness of disconnection and presence of radiological lesion beyond the disconnection margins. Seizure outcome at 6, 12, and 24 months post-surgery was assessed using the Engel Scale (ES). Logistic regression was used to identify relationships between data variables and seizure outcome., Results: 46 children (males = 28, females = 18; age range 0.5-16.6 years) who underwent TPO (n = 32, including a re-do disconnection) or frontal disconnection or resection (n = 15) were identified. Patients in the TPO treatment group had more favourable seizure outcomes than those in the frontal treatment group (ES I-II in 56 %vs 47 % at 6 months, 52 % vs 46 % at 12 months). Presence of the lesion beyond disconnection boundaries and older age at the time of surgery were associated with poorer seizure outcome. Gender, surgery type, completeness of disconnection, scalp EEG findings and underlying pathology were not related to seizure outcome, but subgroup numbers were small., Conclusions: Both TPO and frontal disconnection are effective treatments for selected children with posterior multi-lobar or diffuse frontal lobe epilepsy. Confinement of the MRI lesion within the disconnection margins and a younger age at surgery are associated with favourable seizure outcomes. Further studies are required to elucidate these findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Frontal lobectomy is often used as a surgical treatment for frontal lobe epilepsy, especially when a large epileptogenic zone in the frontal lobe is inferred from preoperative evaluation. The frontal lobe is important for cognitive functions such as executive functions and verbal fluency, but the neuropsychological outcome after a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex has not been studied thoroughly. In the present study, we evaluated neuropsychological outcomes after patients with frontal lobe epilepsy received a frontal or prefrontal lobectomy., Methods: We retrospectively reviewed the data of patients with frontal lobe epilepsy who underwent a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex at 16 years or older from October 2004 to December 2014, with a minimum postoperative follow-up of 24 months. We analyzed and compared neuropsychological outcomes, including executive functions, verbal fluency, intelligence, and memory, before and after the operation., Results: Eighteen patients were 16 years or older and underwent pre- and postoperative (2 years after the operation) neuropsychological evaluations. Patients showed significant deterioration only on the Benton Visual Retention Test. Performance on tests of frontal lobe functions, such as executive function and verbal fluency, showed no significant deterioration., Conclusions: Overall cognitive performance, including functions widely thought to depend on the frontal lobe, is stable after a frontal or prefrontal lobectomy to treat frontal lobe epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Epilepsy is one of the most common chronic neurological diseases. Despite the great variety and prevalence of antiepileptic drug treatments, one-third of epilepsies remain drug resistant. The frontal lobe is extensive, and frontal lobe seizures are difficult to locate, which increases the difficulty of the preoperative localization of the epileptogenic zone., Case Presentation: Two previously healthy girls with refractory frontal lobe epilepsy showed significant perfusion abnormalities in the right frontal lobe using the cerebral blood perfusion (CBF) quantitative analysis system. They became seizure-free after lesionectomy of the frontal lobe by ASL combined with electroencephalography (EEG) rapid localization. The histopathological diagnosis was focal cortical dysplasia (FCD) type IIa and IIb., Conclusions: The positive outcome suggests that the combined use of ASL with EEG could be a beneficial option for the presurgical evaluation of pediatric epilepsy., (© 2021. The Author(s).)

Purpose: Frontal lobe resection (FLR) is the second most common epilepsy surgery procedure in adults. Few studies address neuropsychological consequences after FLR. The aim of this study was to explore patients' and relatives' experiences of cognitive, emotional and social cognitive functioning after frontal lobe epilepsy surgery., Methods: Semi-structured interviews were held with 14 patients having gone through FLR as adults during the years 2000-2016 and 12 of their relatives. Interviews were audio-recorded, transcribed and analyzed with inductive qualitative content analysis., Results: Positive as well as negative consequences were described both by patients and relatives. Feelings of relief and an increased capacity to experience emotions of well-being were mainly experienced as related to seizure freedom. A newfound autonomy and a more grown-up identity as opposed to a self-image based on epilepsy was also highlighted. However, results also showed that even for seizure free patients, FLR could give rise to negative experiences, the most prominent of which were mental fatigue, lowered mood and social withdrawal. Coping strategies included planning ahead to avoid mental exhaustion. Over all, respondents considered that the epilepsy surgery had been a risk well worth taking and that positive consequences outweighed the negative ones., Conclusions: This study shows a range of positive as well as negative outcomes after FLR for epilepsy. The findings indicate that lowered mood and mental fatigue could affect the life situation in a negative way, regardless of seizure outcome. This is important to consider in the preoperative counselling of patients and their families, as well as in the postsurgical follow-up. It is also crucial that the epilepsy surgery team has the possibility to offer rehabilitation and support to families regarding these aspects after surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to better characterize the magnetic resonance imaging (MRI) findings of mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE), a rare clinicopathological entity associated with pharmacoresistance recently described in patients with frontal lobe epilepsy., Methods: We studied 12 patients who underwent epilepsy surgery and whose surgical specimens showed histopathological findings of MOGHE, characterized by preserved cortical lamination, blurred gray-white matter interface due to increased number of oligodendrocytes, and heterotopic neurons in the white matter. The age at MRI evaluation ranged from 11 to 58 years, except for one 4.5-year-old patient., Results: Following a detailed MRI analysis using an in-house protocol, we found abnormalities in all cases. The lesion was circumscribed in the frontal lobe in six (50%) and in the temporal lobe in three (25%) patients. In the remaining three patients (25%), the lesion was multilobar (frontotemporal and temporoparieto-occipital). Cortical thickening was mild in all patients, except in the 4.5-year-old patient, who had pronounced cortical thickening and white matter blurring. We also identified cortical/subcortical hyperintense T2/fluid-attenuated inversion recovery signal associated with gray/white matter blurring in all but one patient. When present, cleft cortical dimple, and deep sulci aided in localizing the lesion. Overall, the MRI findings were like those in focal cortical dysplasia (FCD) Type IIa. Surgical outcome was excellent in five patients (Engel Class I in 25% and II in 17%). The remaining seven patients (58%) had worthwhile seizure reduction (Engle Class III). Incomplete lesion resection was significantly associated with worse outcomes., Significance: MRI findings associated with MOGHE are similar to those described in FCD Type IIa. Although more frequent in the frontal lobe, MOGHE also occurred in the temporal lobe or involved multiple lobes. Multilobar or extensive MOGHE MRI lesions are associated with less favorable surgical outcomes. Because this is a rare condition, multicenter studies are necessary to characterize MOGHE further., (© 2021 International League Against Epilepsy.)

Objective: Patients undergoing frontal lobectomy demonstrate lower seizure-freedom rates than patients undergoing temporal lobectomy and several other resective interventions. We attempted to utilize automated preoperative quantitative analysis of focal and global cortical volume loss to develop predictive volumetric indicators of seizure outcome after frontal lobectomy., Methods: Ninety patients who underwent frontal lobectomy were stratified based on seizure freedom at a mean follow-up time of 3.5 (standard deviation [SD] 2.5) years. Automated quantitative analysis of cortical volume loss organized by distinct brain region and laterality was performed on preoperative T1-weighted magnetic resonance imaging (MRI) studies. Univariate statistical analysis was used to select potential predictors of seizure freedom. Backward variable selection and multivariate logistical regression were used to develop models to predict seizure freedom., Results: Forty-eight of 90 (53.3%) patients were seizure-free at the last follow-up. Several frontal and extrafrontal brain regions demonstrated statistically significant differences in both volumetric cortical volume loss and volumetric asymmetry between the left and right sides in the seizure-free and non-seizure-free cohorts. A final multivariate logistic model utilizing only preoperative quantitative MRI data to predict seizure outcome was developed with a c-statistic of 0.846. Using both preoperative quantitative MRI data and previously validated clinical predictors of seizure outcomes, we developed a model with a c-statistic of 0.897., Significance: This study demonstrates that preoperative cortical volume loss in both frontal and extrafrontal regions can be predictive of seizure outcome after frontal lobectomy, and models can be developed with excellent predictive capabilities using preoperative MRI data. Automated quantitative MRI analysis can be quickly and reliably performed in patients with frontal lobe epilepsy, and further studies may be developed for integration into preoperative risk stratification., (© 2021 International League Against Epilepsy.)

Purpose: Hyperkinetic seizures are described as seizure onset in the frontal or temporal lobe. Additional localizing information is important for diagnostic workup and surgical therapy. We describe diagnostic workup and surgical outcomes in three patients with pharmacoresistant focal emotional seizures with hyperkinetic elements., Methods/results: High-resolution 3 Tesla (T) magnetic resonance imaging (MRI) did not reveal clear-cut lesions. Invasive video-electroencephalography (EEG) with depth electrodes along the cingulate sulcus (bilateral; patients 1 and 3), right; patient 2 provided congruent results for a circumscribed seizure onset zone within the medial frontal lobe (right: patients 1 and 2; left: patient 3). Topectomies were performed in all patients. Histopathology revealed a small focal cortical dysplasia in the three cases (focal cortical dysplasia [FCD] IIA: patient 1; FCD IIB: patients 2 and 3). All patients remained completely seizure-free since surgery (Engel 1A; follow-up: 9-28 months)., Conclusion: Ictal fear associated with hyperkinetic semiology points to a seizure-onset zone within the anteromedial frontal lobe (anterior cingulate gyrus). Ictal semiology is crucial for the placement of depth electrodes, especially in MRI-negative cases. These cases illustrate a clinical advantage to the new International League against Epilepsy (ILAE) seizure classification, emphasizing initial clinical symptoms., Competing Interests: C.G.B. obtained honoraria for speaking engagements from UCB (Monheim, Germany), Desitin (Hamburg, Germany), and Euroimmun (Lübeck, Germany). He received research support from Deutsche Forschungsgemeinschaft (German Research Council, Bonn, Germany) and Gerd-Altenhof-Stiftung (Deutsches Stiftungs-Zentrum, Essen, Germany).T.C. was supported by a stipend from the Epilepsy Academy Berlin-Bethel, and from the von-Bodelschwingh Foundation in Bielefeld-Bethel. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Thieme. All rights reserved.)

The SEEG International Course, organised in 2017, focused on the investigation and surgery of insulo-perisylvian epilepsies. We present one representative complex case that was discussed. The patient had seizures displaying startle/reflex components. He was MRI negative, while other non-invasive investigations offered only partially concordant data. Initial SEEG exploration resulted in an incomplete definition of the epileptogenic zone. A second SEEG followed, which led to a thorough assessment of the seizure onset zone and the epileptic network, localised to the lateral inferior premotor cortex, explaining the incongruent data obtained beforehand. This was the basis of a tailored resection with a favourable outcome. The patient has been seizure-free for five years without any motor nor cognitive deficits, but with pharmacodependence to one AED. The electroclinical reasoning is presented, accompanied by relevant commentaries and recommendations from the tutors [Published with video sequences].

To better understand the electroclinical features and epileptic network of lateral and medial orbitofrontal epilepsy (OFE). We evaluated four patients who had undergone epilepsy surgery. Epileptic foci in two patients originated from the lateral orbitofrontal cortex, and those in the other two originated from the medial orbitofrontal cortex, which was confirmed by stereoelectroencephalography (SEEG). Time-frequency spectrograms were also provided for assistance, and the change in high-frequency energy was superimposed on the 3D reconstructed brain with a colour code in order to more intuitively show the transfer of high-frequency energy as the seizure evolves. All patients underwent SEEG-guided radiofrequency thermocoagulation (RF-TC) or focal resection and achieved satisfactory results. Lateral OFE and medial OFE were relatively independent with regards to clinical symptoms and epileptic network, however, lateral OFE was likely to propagate to the dorsolateral frontal lobe, whereas medial OFE (gyrus rectus) was more likely to propagate to the medial temporal lobe or insular lobe with long duration. There were significant differences in duration (21.17 ± 11.5 vs. 127.22 ± 235.05) and early propagation time (7.92 ± 4.44 vs. 29.0 ± 33.47) between the two origins. A better understanding of the electroclinical features of lateral and medial OFE is helpful to understand their epileptic networks and perform accurate resections in order to protect the cognitive and behavioural functions of patients.

Purpose: Frontal seizures are organized according to anatomo-functional subdivisions of the frontal lobe. Prefrontal seizures have been the subject of few detailed studies to date. The objective of this study was to identify subcategories of prefrontal seizures based on seizure onset quantification and to look for semiological differences., Methods: Consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant prefrontal epilepsy between 2000 and 2018 were included. The different prefrontal regions investigated in our patients were dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), ventromedial prefrontal cortex (VMPFC), and orbitofrontal cortex (OFC). The seizure onset zone (SOZ) was determined from one or two seizures in each patient, using the epileptogenicity index (EI) method. The presence or absence of 16 clinical ictal manifestations was analyzed. Classification of prefrontal networks was performed using the k-means automatic classification method., Results: A total of 51 seizures from 31 patients were analyzed. The optimal clustering was 4 subgroups of prefrontal seizures: a "pure DLPF" group, a "pure VMPF" group, a "pure OFC" group, and a "global prefrontal" group. The first 3 groups showed a mean EI considered epileptogenic (>0.4) only in one predominant structure, while the fourth group showed a high mean EI in almost all prefrontal structures. The median number of epileptogenic structures per seizure (prefrontal or extrafrontal) was 5 for the "global prefrontal" group and 2 for the other groups. We found that the most common signs were altered consciousness, automatisms/stereotypies, integrated gestural motor behavior, and hyperkinetic motor behavior. We found no significant difference in the distribution of ictal signs between the different groups., Conclusion: Our study showed that although most prefrontal seizures manifest as a network of several anatomically distinct structures, we were able to determine a sublobar organization of prefrontal seizure onset with four groups., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection., Methods: We retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally., Results: Thirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm 3 . Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P = .02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths-two seizure-associated and one suicide-were unrelated to surgical procedures., Significance: MRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success., (© 2020 International League Against Epilepsy.)

Although extensive frontal lobectomy (eFL) is a common surgical procedure for intractable frontal lobe epilepsy (FLE), there have been very few reports regarding surgical techniques for eFL. This article provides step-by-step descriptions of our surgical technique for non-lesional FLE. Sixteen patients undergoing eFL were included in this study. The goals were to maximize gray matter removal, including the orbital gyrus and subcallosal area, and to spare the primary motor and premotor cortexes and anterior perforated substance. The eFL consists of three steps: (1) positioning, craniotomy, and exposure; (2) lateral frontal lobe resection; and (3), resection of the rectus gyrus and orbital gyrus. Resection ahead of bregma allows preservation of motor and premotor area function. To remove the orbital gyrus preserving anterior perforated substance, it is essential to visualize the olfactory trigone beneath the pia. It is important to observe the surface of the contralateral medial frontal lobe for complete removal of the subcallosal area of the frontal lobe. Thirteen patients (81.25%) became seizure-free and three patients (18.75%) continued to have seizures. None of the patients showed any complications. The eFL is a good surgical technique for the treatment of intractable non-lesional FLE. For treatment of epilepsy by eFL, it is important to resect the non-eloquent area of the frontal lobe as much as possible with preservation of the eloquent cortex.

There is accumulating evidence for considerable overlap in preoperatively affected cognitive functions in patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). The current study investigated whether it is possible to differentiate between patients with FLE and TLE prior to surgery, based on measures of verbal memory and executive functioning. Furthermore, the postoperative cognitive development was compared. Pre- and postoperative data from 109 patients with FLE and 194 patients with TLE were retrospectively analyzed. Preoperatively, there were no differences in verbal memory, and postoperatively, no distinctive cognitive change was found between patients with FLE and TLE. However, patients with FLE performed worse on a cognitive switching task. Notably, irrespective of localization, patients with a presumed epileptogenic area in the language-dominant hemisphere performed worse than patients with seizures that originated in the nonlanguage-dominant hemisphere on measures of verbal memory, both pre- and postoperatively. In sum, the results suggest that verbal memory scores may be less valuable for differentiation between TLE and FLE, while measures of executive functioning may help identify patients with FLE. Additionally, rather than the localization, epilepsy lateralization critically impacts the evaluation of verbal memory functioning in both TLE and FLE. The results are discussed in light of the current frameworks of functional disturbances in epileptic networks., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Frontal lobe epilepsy (FLE) surgery is the second most common focal resective surgery for drug-resistant epilepsy. Not many studies are available regarding the long-term surgical outcome of FLE. We studied the longitudinal outcome and predictors of seizure outcome following FLE surgery in a sizeable cohort of patients., Materials & Methods: A total of 73 consecutive patients who underwent FLE surgery between January 1997 and May 2015 with a minimum follow-up of 1 year (range 1-16 years) were studied. Primary outcome was seizure freedom at last follow-up (Engel Class IA). "Seizure freedom" separately was defined as absence of seizures till last follow-up. Outcome predictors were subjected to multivariate analysis. Using Kaplan-Meier curve, we assessed the post-operative seizure freedom over time., Results: Twenty-five patients (34%) were seizure-free till last follow-up. The seizure freedom was 45%, 34%, 26%, 20% and 14% at the end of 1st, 2nd, 3rd, 4th and 5th post-operative year, respectively. Engel class I outcomes were 48%, 41%, 56%, 57% and 53% at end of 1st, 2nd, 3rd, 4th and 5th post-operative year, respectively. Predictors of seizure recurrence on multivariate analysis were older age at surgery (P = 0.032), longer duration of epilepsy (P = 0.031), presence of interictal epileptiform discharges in post-operative EEG on 7th day (P = 0.005), 3 months (P = 0.005) and 1 year (P = 0.0179). In subgroup analysis, duration of epilepsy of less than 2 years before surgery was a significant predictor for achieving seizure freedom (P = 0.029)., Conclusions: These results emphasize early surgery for better outcome in frontal lobe epilepsy. Post-operative EEG remained a good predictor for long-term outcome., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Early damage to the ventromedial prefrontal cortex (VM) has been associated with impaired behavioural functioning in children without epilepsy, yet behaviour in children with epilepsy and VM lesions has not been investigated. The primary aim of this study was to examine behavioural outcomes in children with epilepsy emanating from the VM preoperatively and one year after epilepsy surgery compared to the general population and matched epilepsy controls. Behavioural outcomes were defined as comprising both problems and competencies (i.e. social, school and co-curricular performance). A secondary aim was to examine whether seizure outcome, number of antiepileptic drugs (AEDs), or age at surgery related to behavioural outcomes. Ratings on the Child Behavior Checklist were examined preoperatively and 1 year after surgery for 20 children with epilepsy who had undergone surgical resection of the VM (N = 10) or temporal lobe (TL, N = 10). VM and TL groups were comparable on Full Scale IQ (40-101), age of seizure onset (0.5-9.0 years), age at surgery (3.1-16.9 years), seizure laterality (5 left in each group), age at assessments, sex (3 female in VM group, 2 female in TL group) and seizure outcome (7 seizure free in VM group, 6 seizure free in TL group). The VM group had significantly elevated behaviour problems (i.e. withdrawn, thought, social and attention problems) and reduced competencies (i.e. social and school) compared to the general population before and after surgery. VM and TL cases did not differ on any behaviour problem scales pre or postoperatively and neither group showed significant change in functioning over time; however, VM patients had significantly lower total competence than TL patients postoperatively. A significant seizure outcome × time interaction was observed: children who were seizure free following surgery (collapsed across surgical site) showed an improvement in total behaviour problems and aggression at 1 year follow-up, whereas children with ongoing seizures showed a deterioration in these domains. In conclusion, VM lesions in children with epilepsy are associated with behavioural problems but their profile does not differ from that of children with temporal lobe epilepsy. These results are consistent with the concept that seizures arise from epileptogenic networks that may affect multiple cortical areas, even when onset is in a focal site., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

When performing pre-surgical evaluation of patients with refractory epilepsy, the analysis of seizure semiology is one of the key elements used to generate a hypothesis about the location of the epileptogenic zone. Ictal kissing is a very rarely observed ictal automatism described in patients with temporal lobe epilepsy. We present a 62-year-old man who was referred to our epilepsy centre for comprehensive evaluation. During prolonged video-EEG monitoring, six focal-onset hyperkinetic seizures were registered. In five seizures, the patient repeatedly produced sonorous kisses "into the air". Initial ictal EEG pattern consisted of rhythmic theta or alpha activity at the right fronto-polar and fronto-medial electrodes. MRI depicted focal cortical dysplasia located in the right prefrontal medial cortex. This case suggests that ictal kissing can also occur in the setting of right frontal lobe epilepsy; we therefore believe that this observation expands the anatomo-clinical correlation for this rare ictal automatism. [Published with video sequences].

Background and Objectives: Ictal epileptic headache is a rare form of painful seizure, habitually consisting of migrainous or tension-type headache. We describe a case of a patient with short-lasting, severe retroorbital pain attacks caused by frontal lobe epilepsy., Case Report: A 25-year-old male patient presented with recurrent attacks of paroxysmal, short-lasting, excruciating left periorbital and facial pain mainly occurring from sleep. After intracranial EEG exploration and resection of a right prefrontal focal cortical dysplasia, long-term seizure and headache remission was obtained., Discussion: Our case extends the clinical and neuroanatomical spectrum of ictal epileptic headache and suggests that long-term remission can be obtained by resective epilepsy surgery. It also reinforces the role of the prefrontal cortex in the pain matrix and pain generation., Conclusion: Despite its rarity, ictal epileptic headache should be suspected in selected patients, particularly those with other ictal symptoms and signs, history of epileptic seizures, or neuroimaging abnormalities.

Objectives: The aims of this study were to determine the rate of dysfunctional personality patterns before and after epilepsy surgery, their types, and the importance of the epileptogenic zone in a sample of people with refractory epilepsy., Methods: We conducted an ambispective observational study, including refractory epilepsy surgery candidates. Demographic, psychiatric, and neurological data were recorded. Evaluation of personality was made using the Millon Clinical Multiaxial Inventory-II (MCMI-II). Presurgical predictors of personality patterns were determined using a linear regression model. The proportion of patients with dysfunctional personality patterns, before and after surgery, was compared using the Mcnemar's test. Then a generalized estimating equation model was performed to include predictors of changes in this rate., Results: One hundred and ninety-nine participants were included. Seventy percent had a dysfunctional personality pattern before surgery. After surgery, this percentage dropped to 58%. The difference was statistically significant after adjusting for potential confounders (p = 0.013). The most common types were Cluster C personality patterns. Temporal epileptogenic zone was a significant predictor of higher scores of the Avoidant (Coef. 11.8; Confidence Interval (CI) -0.59 23.7; p = 0.051) and Compulsive (Coef. 9.55; CI 2.48 16.6; p = 0.008) personality patterns and lower scores of Histrionic (Coef. -11.4; CI -21.2 -1.55; p = 0.024) and Antisocial (Coef. -8.4; CI -15.6 -1.25; p = 0.022) personality patterns, compared to extratemporal epileptogenic zone., Conclusion: People with refractory epilepsy have high rates of dysfunctional personality patterns. These patterns differ according to the epileptogenic zone., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Ictal semiology complements ictal EEG in identifying the likely epileptogenic zone. Ictal turning prone (ITP) with body turning of 90 ° or more can be seen with frontal lobe epilepsies. The aim of our study was to evaluate the localizing value of ITP in a general population of patients undergoing long term video-EEG monitoring., Methods: We reviewed our epilepsy monitoring unit database for adult patients with recorded habitual seizures with ITP. All 16 patients identified had continuous video-EEG monitoring using standard scalp electrodes; eight patients also had intracranial EEG monitoring. We only included focal seizures without evolution to bilateral tonic-clonic activity., Results: We identified 16 patients with ITP, mean age of 32.5 years (range 18-50). ITP was consistently seen in at least one focal impaired awareness seizure of all patients. Ictal onset zone on scalp EEG was left temporal in five, right temporal in three, left frontal convexity in two, right frontal convexity in two, probable right medial frontal in three and probable left medial frontal in one patient. Direction of ITP was uni-directional in 12 patients while 4 patients had ITP in opposite direction in different seizures. Nine patients underwent epilepsy surgery; five patients had Engel class I outcome and four patients had Engel class III outcome., Conclusions: Ictal turning prone does not have a consistent single localizing or lateralizing value and can be seen with various epileptogenic zones including medial frontal, lateral frontal or temporal. ITP direction can vary even with a single epileptogenic zone., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To report clinical experience with presurgical evaluation in patients with insulo-opercular epilepsy. Quantitative analysis on PET imaging and stereoelectroencephalography (SEEG) signals was used to summarize their electroclinical features., Methods: Twenty-two patients with focal epilepsy arising from the insular and/or opercular cortex according to SEEG were retrospectively analyzed. Presurgical noninvasive data were analyzed in detail. Interictal PET data of patients were then statistically compared with those of healthy controls to identify the interictal hypometabolic network. The epileptogenicity index (EI) of ictal SEEG signal was computed to identify areas of spread at the beginning of seizure onset., Results: Focal tonic seizures of the face and/or neck (16/22, 73%) were the most prevalent early objective signs. Epileptic discharges in the interictal and ictal scalp-EEG mostly showed an ipsilateral perisylvian distribution. Statistical analysis of interictal PET showed significant hypometabolism in the insular lobe, central operculum, supplementary motor area, middle cingulate cortex, bilateral caudate nuclei, and putamen. According to the EI analysis, insulo-opercular epilepsy could be classified as insulo-opercular epilepsy (50%), opercular epilepsy (41%), and insular cortex epilepsy (9%)., Significance: Clinical diagnosis of insulo-opercular epilepsy is challenging because of its complex seizure semiology and nonlocalizing discharges on scalp-EEG. A common hypometabolic network involving the insulo-opercular cortex, mesial frontal cortex and subcortical nuclei may be involved in the organization of the insulo-opercular epilepsy network. Furthermore, quantified SEEG analysis suggested that pure insular epilepsy is rare, and the close connection between insular and opercular cortex necessitates SEEG implantation to define the epileptogenic zone., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

We provide an overview of the surgical outcome of extra-hypothalamic epilepsies with gelastic seizures based on an original case report and a summary of the literature. Twenty-two articles providing information on the outcome of resective surgery in 39 patients with extra-hypothalamic gelastic seizures from the temporal (19 patients) or frontal lobe (20 patients) were selected. We add another case of temporal lobe gelastic seizures to the literature with a video demonstrating the mirthful component of this patient's laughing seizures. Drug-refractory cases of gelastic seizures from the temporal or frontal lobes are amenable to surgical treatment following thorough investigation with imaging, as well as scalp and intracranial EEG.

We report the case of a patient with epilepsy who described shame and embarrassment at the beginning of his seizures. Non-invasive and invasive presurgical investigations led to resection of the polar and ventromedial portions of the right frontal lobe. Following the surgery, the patient continued to have seizures, albeit only nocturnal and with no clear aura. Subsequent removal of the right anterior insula at the junction with the frontal operculum and the posterior orbitofrontal cortex led to seizure freedom, but the patient reported a loss of motivation and stamina and was declared unfit for work. The underlying network of negative moral emotions is briefly discussed.

Recognition of insular epilepsy may sometimes be challenging due to the rapid speed at which insular seizures can spread throughout the cortex via extensive connections to surrounding cortices. The spectrum weighted adaptive directed transfer function, a multivariate causality-based effective connectivity measure, was applied to intracranial electroencephalography recordings to identify generators of seizure activity. A non-parametric test based on surrogate data testing was used to validate statistical significance of causal relations. Outflow and inflow of seizure activity were extracted from the computed transfer matrix. Recorded data of 21 seizures from seven patients were analyzed including five who were rendered seizure-free after operculo-insular resection. Effective connectivity analysis of 7 s following electrical onset confirmed an operculo-insular seizure origin in 5 patients with a good post-operative seizure outcome, and for whom the resected region was sampled by intracranial electroencephalography contacts. Different or additional seizure foci were identified in 2 patients with a bad post-operative seizure outcome. Findings highlight the feasibility of accurate operculo-insular seizure foci localization based on quantitative approaches., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hyperkinetic seizures are usually associated with frontal lobe epilepsy. However, some patients have hyperkinetic seizures of temporal lobe origin. The semiological differences in hyperkinetic seizures between frontal and temporal lobe epilepsy have not been well studied. Here, we retrospectively assessed ictal semiology in order to distinguish between hyperkinetic seizures of frontal lobe origin and those of temporal lobe origin. We retrospectively reviewed data on patients who had undergone surgery for hyperkinetic seizures of temporal or frontal lobe origin and achieved favourable seizure outcomes (Engel Class I) with a minimum postoperative follow-up of 24 months. We reviewed seizure histories, imaging reports, video-EEG monitoring data, operative records, and pathological findings. We analysed and compared the hyperkinetic semiology of video-recorded seizures of temporal lobe origin and those of frontal lobe origin. Forty hyperkinetic seizures in eight patients (seven adult patients and one 12-year-old patient) with temporal lobe epilepsy and 45 hyperkinetic seizures in nine patients (eight adult patients and one 16-year-old patient) with frontal lobe epilepsy were analysed. Emotional facial expressions (such as fear, laughing, or anger), bilateral forceful elbow flexion, bilateral forceful grasping, facial flushing, and bilateral facial contraction were observed significantly more frequently in seizures of frontal lobe origin. Oroalimentary automatisms, seizures during wakefulness, salivation, and bilateral drop of the corners of the mouth were observed significantly more frequently in seizures of temporal lobe origin. Observation of a number of signs during hyperkinetic manifestations may help to predict whether a seizure originates from the frontal lobe or the temporal lobe.

Surgical resection of the epileptogenic zone within the frontal lobe can be a very effective treatment for medically refractory epilepsy originating from this area. While much of the frontal lobe consists of highly eloquent tissue, surgery is not necessarily contraindicated as long as the epileptogenic zone is well-localized and the tissue resected is limited. Resection of the primary motor cortex was described by Victor Horsley in the 19th century and was used frequently in the early 20th century for a variety of neurological disorders including epilepsy; improvements in surgical techniques and mapping has led to a resurgence of its use in the past few decades. Although many surgeons are hesitant to resect tissue adjacent to the primary hand area based on fears of new motor deficits, there is extensive evidence that focal resections are well-tolerated over the long-term with residual weakness that is fairly mild: some patients experience postoperative weakness, including hemiparesis, but a stereotypical recovery of strength from proximal to distal muscles occurs over months, and only one quarter will have a permanent neurologic deficit, usually consisting of difficulty with fine motor movements. The main alternative to surgical resection is subpial transection, characterized by a small decrease in postoperative deficits and significantly worse seizure outcomes. The treatment of patients with seizures originating from this region requires a solid understanding of the structural and functional anatomy of the frontal lobe., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery., Method: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome., Results: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357)., Conclusion: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We aimed to investigate the possible predictive factors and longitudinal change in long-term surgical outcome after refractory frontal lobe epilepsy surgery., Methods: We retrospectively reviewed 82 patients who underwent frontal lobe resection. Invasive monitoring was performed in 43 patients. All patients were followed-up for a minimum of 3 years after surgery. Univariate and multivariate analyses were used to evaluate the predictors. The Kaplan-Meier survival curve showed the estimated probability of complete seizure freedom, and a favorable outcome was defined as Engel class I at the last follow-up., Results: The estimated probability of complete seizure freedom was 57.3% at 1 year postoperatively, 51.2% at 2 years, and 50.0% at 5 years. Factors predictive of worse long-term outcome were lack of a lesion in the frontal lobe on magnetic resonance imaging, generalized/nonlocalized ictal discharge, use of subdural grids, and acute postoperative seizure (APOS). After the surgery, 44 patients (53.7%) had seizures at any time during the first 2 years. Five of 44 patients had seizure freedom at the last follow-up. After a seizure-free period of at least 6 months, seizure recurred in 6 patients by 6 months to 1 year (early recurrence) and in 9 patients by 1-3 years (late recurrence). Eight of 43 (18.6%) seizure-free patients had discontinued drugs., Conclusions: The overall seizure outcome after surgery changed most during the first 2 years. The presence of frontal focal lesions and ictal frontal rhythm predicted favorable outcome. However, APOS was predictive of early epilepsy recurrence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neuroinflammation has been shown to constitute a crucial mechanism in the pathophysiology of epileptic brain and several genes of inflammatory mediators have been detected in surgically resected hippocampus tissue but not in non-related seizure brain regions. Interestingly, it has been reported an olfactory dysfunction in frontal lobe epilepsy (FLE). Our aim was to quantify the gene expression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs (OB) tissue from FLE patients. RNA was isolated from OB resection of FLE patients and autopsy subjects without any neurological disease (n = 7, each). After cDNA synthesis, we performed qPCR for interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor κB p65 (RELA), Toll-like receptor 4 (TLR 4), its agonist high mobility group box 1 (HMGB 1) as well nitric oxide synthase isozymes (NOS 1, 2 and 3). We found a significant increase in gene expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), TLR4 receptor and in its agonist HMGB1 and the downstream transcription factor NFκB p65. Moreover, we observed an increase of both NOS1 and NOS3 and a slightly increase of NOS2; however, it was not significant. Our study describes the overexpression of inflammatory-related genes and NOS isozymes in OB from FLE patients. Even though, the number of patients was limited, our findings could point out that neuroinflammation and nitrosative stress-related genes in the OB could be produced in general manner in all brain regions and thus contribute in part, to the olfactory dysfunction observed in FLE patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Stereotactic laser ablation (SLA) is being increasingly used to treat refractory focal epilepsy, especially mesial temporal lobe epilepsy. However, emerging evidence suggests it can be used for extratemporal lobe epilepsy as well.The authors report the case of a 17-year-old male who presented with refractory nocturnal seizures characterized by bilateral arms stiffening or rhythmic jerking lasting several seconds. Semiology suggested an epileptogenic zone close to one of the supplementary sensory motor areas. Electroencephalography showed seizures arising from the central region without consistent lateralization. Brain imaging showed no abnormality. An invasive evaluation using bilateral stereoelectroencephalography (SEEG) was utilized in 2 steps, first to establish the laterality of seizures, and second to further cover the mesial cingulate region of the right hemisphere. Seizures arose from the middle portion of the right cingulate gyrus. Extraoperative electrical mapping revealed that the seizure onset zone was adjacent to eloquent motor areas. SLA targeting the right midcingulate gyrus was performed. The patient has remained seizure free since immediately after the procedure with no postoperative deficits (follow-up of 17 months).This case highlights the utility of SEEG in evaluating difficult-to-localize, focal epilepsy. It also demonstrates that the use of SLA can be extended to nonlesional, extratemporal epilepsies.

Objective: The diagnosis and treatment of insular and insulo-opercular epilepsy remain underexplored because the insula is covered by the insulo-opercular and a dense vascular curtain. Stereoelectro-encephalography (SEEG) is a reliable and recommended technique for locating the epileptic zone, especially in insular and insulo-opercular regions (Isnard et al., 2000, 2004). Bipolar electro-coagulation with cortextomy is an alternative therapy for treating drug-resistant epilepsy and is more convenient and less likely to cause adverse complications. We report 20 patients with insular and insulo-opercular epilepsy diagnosed through SEEG who underwent surgical treatment via bipolar electro-coagulation with cortextomy. The outcomes and findings are presented as a retrospective analysis (Cui et al., 2012; Zhai et al., 2015)., Method: We performed a retrospective analysis of 20 insular and insulo-opercular epilepsy patients. All patients involved in the analysis had undergone a comprehensive presurgical evaluation, including video electro-encephalographic recordings (at least 1 insultus), SEEG (at least 3 electrodes placed at insular depth), magnetic resonance imaging, positron emission tomography, and magneto-encephalography. All patients underwent bipolar electro-coagulation with cortextomy surgery. The follow-up time was over 24 months., Result: After bipolar electro-coagulation with cortextomy surgical treatment, 16 of the 20 patients (80.0%) were seizure free (Engel class I), and all patients achieved satisfactory seizure control (Engel class I-III) with a mean follow-up of 29.6 months (range, 24-39 months). Histopathological findings demonstrated focal cortical dysplasia in 14 patients (70.0%), neuro-damage in 3 patients (15.0%), ganglioglioma in 2 patients (10.0%), and gliosis in 1 patient (5.0%). Sixteen of the 20 patients reported no complications (80.0%), 3 exhibited temporary complications that recovered within 3 months (15.0%), and 1 patient experienced permanent complications (5.0%)., Significance: Bipolar electro-coagulation with cortextomy of the insular and insulo-opercular cortex explored by SEEG findings can be performed safely and resulted in satisfactory seizure control., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Resective surgery established treatment for pharmacoresistant frontal lobe epilepsy (FLE), but seizure outcome and prognostic indicators are poorly characterized and vary between studies., Objective: To study long-term seizure outcome and identify prognostic factors., Methods: We retrospectively analyzed 42 FLE patients having undergone surgical resection, mostly preceded by invasive recordings with stereoelectroencephalography (SEEG). Postsurgical outcome up to 10-yr follow-up and prognostic indicators were analyzed using Kaplan-Meier analysis and multivariate and conditional inference procedures., Results: At the time of last follow-up, 57.1% of patients were seizure-free. The estimated chance of seizure freedom was 67% (95% confidence interval [CI]: 54-83) at 6 mo, 59% (95% CI: 46-76) at 1 yr, 53% (95% CI: 40-71) at 2 yr, and 46% (95% CI: 32-66) at 5 yr. Most relapses (83%) occurred within the first 12 mo. Multivariate analysis showed that completeness of resection of the epileptogenic zone (EZ) as defined by SEEG was the main predictor of seizure outcome. According to conditional inference trees, in patients with complete resection of the EZ, focal cortical dysplasia as etiology and focal EZ were positive prognostic indicators. No difference in outcome was found in patients with positive vs negative magnetic resonance imaging., Conclusion: Surgical resection in drug-resistant FLE can be a successful therapeutic approach, even in the absence of neuroradiologically visible lesions. SEEG may be highly useful in both nonlesional and lesional FLE cases, because complete resection of the EZ as defined by SEEG is associated with better prognosis.

Background: Although frontal lobe resections account for one-third of intralobar resections in pediatric epilepsy surgery, there is a dearth of information regarding long-term seizure freedom, overall cognitive and adaptive functioning., Objective: To identify outcome predictors and define the appropriate timing for surgery., Methods: We retrospectively analyzed the data of 75 consecutive patients aged 10.0 ± 4.9 yr at surgery that had an 8.1 yr mean follow-up., Results: Etiology comprised focal cortical dysplasia (FCD) in 71% and benign tumors in 16% cases. All patients but one had a magnetic resonance imaging-visible lesion. At last follow-up, 63% patients remained seizure-free and 37% had discontinued antiepileptic drugs. Presurgical predictors of seizure freedom were a shorter epilepsy duration, strictly regional epileptic discharges in electroencephalography (EEG), and an epileptogenic zone and/or lesion distant from eloquent cortex. Postsurgical predictors were the completeness of resection and the lack of early postoperative seizures or epileptic discharges in EEG. Higher presurgical overall cognitive and adaptive functioning was related to later epilepsy onset and to a sublobar epileptogenic zone and/or lesion. Following surgery, scores remained stable in the majority of patients. Postsurgical gains were determined by higher presurgical performance and tumors vs FCD., Conclusion: Our findings highlight the favorable long-term outcomes following frontal lobe epilepsy surgery in childhood and adolescence and underline the importance of early surgical intervention in selected candidates. Early postsurgical relapses and epileptic discharges in EEG constitute key markers of treatment failure and should prompt timely reevaluation. Postsurgical overall cognitive and adaptive functioning is stable in most patients, whereas those with benign tumors have higher chances of improvement.

Background: Orbitofrontal epilepsy (OFE) is less known and is poorly characterized in comparison with temporal lobe epilepsy, partly because it is rare and possibly because it is unrecognized and therefore underestimated., Objective: This paper aimed to better characterize seizure semiology, presurgical findings, and surgical outcomes in patients with OFE., Methods: We retrospectively reviewed all confidently established OFE cases from six Canadian epilepsy monitoring units between 1988 and 2014, and in the literature between 1972 and 2017. Inclusion criteria were identification of an epileptogenic lesion localized in the OFC or if the patient was seizure-free after surgical removal of the OFC in nonlesional cases., Results: Sixteen cases were identified from our databases. Fifty percent had predominantly sleep-related seizures; 56% had no aura (the remaining had nonspecific or vegetative auras), and 62.5% featured hypermotor (mostly hyperkinetic) behaviors. Interictal epileptiform discharges over frontal and temporal derivations always allowed lateralization. Magnetic resonance imaging (MRI) identified an orbitofrontal lesion in 8/16, positron emission tomography (PET) identified a hypometabolism extending outside the orbital cortex in 4/9, ictal single-photon emission computed tomography (SPECT) identified an orbital hyperperfusion in 1/5, magnetoencephalography (MEG) identified lateral orbital sources in 2/4, and intracranial electroencephalography (EEG) identified an orbitofrontal onset in 9/10. Fourteen patients underwent surgery, all reaching a favorable outcome (71.4% Engel 1; 28.6% Engel 2; mean FU=5.6years). Pre- and postoperative neuropsychological assessments revealed heterogeneous findings. Our review of literature identified 71 possible cases of OFE, 32 with confident focus localization. Extracted data from these cumulated cases supported observations made from our case series., Conclusions: Orbitofrontal epilepsy should be suspected with sleep-related, hyperkinetic seizures with no specific aura, and frontotemporal interictal discharges. Several patients have nonmotor seizures with or without auras which may resemble temporal lobe seizures. Postoperative seizure outcome was favorable, but there is inherent bias as we only included patients with a seizure-free outcome if the MRI was negative. A larger study is required to address identified gaps in knowledge such as identifying discriminative features between medial and lateral OFE, evaluating the value of more recent diagnostic tools, and assessing the neuropsychological outcome of orbital epilepsy surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)